1. Field of Invention
This invention relates to a method for eradicating weeds using pyrrolidineone derivatives of herbicidal tenuazonic acid (3-acetyl-5-sec-butyl-4-hydroxy-3-pyrrolin-2-one).
2. Description of the Related Art
Tenuazonic acid (formula name 3-acetyl-5-sec-butyl-4-hydroxy-3-pyrrolin-2-one) is a strong phytotoxin isolated, purified, and identified from metabolites of Alternaria Alternata by Qiang Sheng et al. It is isolated from a crude mixture of metabolites by the extraction of the fermentation fluid. Due to the low yield (0.0005%) and high cost of fermentation, it is very urgent to develop a synthetic process of the compound.
3-Acetyl-4-hydroxy-5-tert-butylpyrroline-2-ketone is a heterocyclic compound containing carbonyl and hydroxyl functional groups. The lactam that is a part of the heterocyclic ring is the most important functional group. The hydrophobic side chain also plays an important role in its herbicidal activity.
The compound is very effective at killing monocotyledon weeds (such as common crabgrass and barnyardgrass) and dicotyledonous weeds including Crofton weeds at a concentration of 50 μg/mL. It has the potential to become a biological herbicide (CN Pat. Appl. No. 200510038263.2; CN Pat. No. 1644046). However, the low yield and high cost associated with the fermentation process prevents large-scale production of this compound.
A patent (WO1994/01401) discloses 3-benzoylpyrrolidine-2,4-dione derivatives and their herbicidal activity.
CN. Pat. Pub. No. 1676515A made claims based on the fact that some triketones inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD), which is a key enzyme responsible for biosynthesis of plastoquinone and α-tocopherol. If the biosynthesis of plastoquinone and C-tocopherol is blocked, it will impact the biosynthesis of carotenoids. Therefore, HPPD inhibitor and carotenoid inhibitors have similar functions. This type of compounds has similar structural modification and synthesis, i.e., the existence of N-substituent. The major representative of this type of herbicides is sulfentrazone, isoxazole herbicide, and pyridine type herbicides. It is reported that tenuazonic acid copper salt has a slight inhibition to HPPD (Meazza et al., 2002). With only hydrogen attached to nitrogen, no other substituents, it is obvious that 3-acetyl-4-hydroxy-5-tert-butylpyrroline-2-ketone has a totally different mechanism of action.
Study on the mechanism of action of 3-acetyl-4-hydroxy-5-tert-butylpyrroline 2-ketone has shown that the phytotoxin clearly inhibits the photosynthesis of plants. Its inhibition to Hill reaction is much higher than the typical photosynthetic inhibitor (herbicide), such as 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). In addition, there is no adverse effect to other parts of the cells. The compound blocks electron flow from QA to QB in the photosystem II, but has no effect on the donor of photosystem II, photosystem I and other parts of chloroplasts, which was the first time such effects were observed among known phytotoxins produced by fungus Alternaria alternata. 
It is believed that the toxin interacts with D1 protein by competing with QB for the binding site and thus inhibits the electron transfer. Therefore, it is an inhibitory phytotoxin of photosystem II. Based on the discovery of this mechanism, the molecular structure of tenuazonic acid has heretofore been modified to yield a series of new herbicidal molecules (See CN Appl. Nos. 200510094521.9 and 200610038765.X, and CN Pat Pub No. CN1752075).
Many photosystem II inhibitors have successfully become commercial herbicides in the field of herbicides, such as s-triazines, triazinones and phenols, etc. There are two advantages associated with the photosystem II inhibitors: first, since photosynthesis is a common phenomenon among plants, and inhibition is specific to the plants, the toxicity to animals is low, thus this type of herbicides possesses the characteristics of high efficacy and low toxicity. Second, with the development of transgenic technology, there are 67,700,000 hectares of farm land that grow transgenic crops globally and greater than 80% of these crops are herbicide-resistant transgenic (based on Monsanto's 2003 data).
The photosynthetic inhibitors herbicides have a growing share of the herbicides market. With combination of new herbicides and transgenic agricultural products, the chemical pollution to the environment has been greatly reduced. Since the photosynthetic inhibition is the only effect for 3-acetyl-5-sec-butyl-4-hydroxy-3-pyrrolin-2-one on the plant cells, this type of herbicide with high potency, quick action, broad-spectrum, simple structure, and easy synthesis will have a bright future.
There are many types of photosystem II inhibitors according to their chemical structures such as ureas, pyridines, triazinones, pyridazinones, dinitrophenols and cyanophenols, etc. They can be divided into two main groups such as ureas/triazine and phenol. The first type (classical photosystem II inhibitors) can be represented as N—C═X (X stands for O or N atom, not sulfur atom), i.e. atrazine, metribuzin, phemedipham, terbutryand, N-(3,4-dichlorophenyl)-N′-methylurea (DCMU) et al. The second type is phenolic herbicide, including ioxynil, dinoseb and 2-iodo-4-nitro-6-isobutylphenol, etc.
The common feature of the second type of herbicide is that the molecules contain at least one carbonyl oxygen or hydroxy oxygen and a long hydrophobic hydrocarbon side-chain. Most of these herbicides form a hydrogen bond between the carbonyl hydrogen and the D1 protein of photosystem II, which enables them to successfully compete with plastoquinone QB (secondary electron acceptor), thereby blocking electron transfer from QA to QB and leading to the inhibition of photosynthetic process of the plant.
Only a small number of herbicides form hydrogen bond between hydroxyl oxygen and D1 protein and successfully block photosynthetic process. The structure of the hydrophobic hydrocarbon side-chain (number of carbon and chain length) also influences herbicidal activity. Obviously, the binding site, binding manner, and possible binding region of herbicides to D1 protein determine the strength of herbicidal activity. Based on the chemical structure, 3-acetyl-5-sec-butyl-4-hydroxy-3-pyrrolin-2-one belongs to the group of photosystem II inhibitor (containing N—C═O). Unlike the classical herbicides mentioned above, there are no literatures that describe the mechanism of action of this compound to photosynthesis. Therefore, it might be a new type of photosystem II inhibitor.
3-acetyl-5-sec-butyl-4-hydroxy-3-pyrrolin-2-one has moderate toxicity of 200 mg/kg to rat and moderate level phytotoxicity, which is acceptable in light of its high biological activity. However, its toxicity level may be reduced through modification of its chemical structure.